A biogenetic approach to the synthesis of phenolic natural products is proposed. The general procedure involves synthesis of poly-beta-carbonyl compounds. In many cases one or more of the carbonyl groups will be protected as a ketal or other derivative to enhance the stability of the compound or to direct subsequent cyclizations. Conditions will be sought by which cyclizations can be effected that will give natural products by processes duplicating the biosynthetic schemes. The whole range of polyketide metabolites will be investigated bu particular emphasis will be placed on synthetic approaches to the pretetramids which are precursors of the tetracycline antibiotics. The synthetic route will be used to prepare structural variants of the pretetramids and these will be employed in fermentations for preparation of novel semi-synthetic tetracyclines.